Variant 2-28529405-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_153021.5(PLB1):c.414T>C(p.Ala138=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,594,000 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00078 ( 6 hom. )

Consequence

PLB1
NM_153021.5 splice_region, synonymous

Scores

Splicing: ADA: 0.00002612

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.369

Variant links:

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

PLB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-28529405-T-C is Benign according to our data. Variant chr2-28529405-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 728995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.369 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLB1	NM_153021.5 linkuse as main transcript	c.414T>C	p.Ala138=	splice_region_variant, synonymous_variant	7/58	ENST00000327757.10
PLB1	NM_001170585.2 linkuse as main transcript	c.414T>C	p.Ala138=	splice_region_variant, synonymous_variant	7/57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000327757.10 linkuse as main transcript	c.414T>C	p.Ala138=	splice_region_variant, synonymous_variant	7/58	1	NM_153021.5	P1	Q6P1J6-1
PLB1	ENST00000422425.6 linkuse as main transcript	c.414T>C	p.Ala138=	splice_region_variant, synonymous_variant	7/57	1			Q6P1J6-3
PLB1	ENST00000404858.5 linkuse as main transcript	c.411T>C	p.Ala137=	splice_region_variant, synonymous_variant	7/57	1
PLB1	ENST00000416713.5 linkuse as main transcript	c.246T>C	p.Ala82=	splice_region_variant, synonymous_variant	7/11	5

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

338

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00117

AC:

294

AN:

251338

Hom.:

AF XY:

0.00113

AC XY:

153

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00621

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000792

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000780

AC:

1125

AN:

1441690

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

562

AN XY:

718456

show subpopulations

Gnomad4 AFR exome

AF:

0.00479

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.000845

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000630

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152310

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00539

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00152

Hom.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00154

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	PLB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.98

DANN

Benign

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over